As a high efficient and broad spectrum bactericide, azoxystrobin is widely used for preventing and treating a variety of plant diseases.
WO92/08703 disclosed an azoxystrobin synthesis method. In that method, a chemical compound with a structure represented by formula (2) has an etherification reaction with 2-hydroxyphenol and potassium carbonate in a polar solvent (in particular N,N-dimethyl formamide), with a copper halide as the catalyst; after the reaction, the reaction mixture is filtered and washed with N,N-dimethyl formamide, and is treated by reduced pressure distillation under 70° C. water bath condition to obtain a crude product; then, the crude product is dissolved in methanol by refluxing, and is cooled to 0-5° C. for crystallization; finally, the crystallized product is washed with petroleum ether and vacuum-dried at 50° C. to obtain a final product.

In the method disclosed in patent document WO2006/114572, allow a chemical compound with a structure represented by formula (2) to react with 2-cyanophenol and an acid acceptor in an inert solvent or diluent, with 1,4-diazabicyclo[2.2.2]-octane as the catalyst; after the reaction, the reaction mixture is cooled to 70-75° C. and keep the temperature by adding water slowly into the reaction mixture, and stir the reaction mixture at 75° C., kept standing, and then remove the aqueous phase; next, water is added into the reaction mixture again and then remove the aqueous phase, to obtain an organic phase that contains the product.
In the method disclosed in patent document WO2008/075341, allow a chemical compound with a structure represented by formula (2) to react with 2-cyanophenol and a hydroxide or carbonate of an alkali metal in a solvent (preferably DMF, DMAA, or DMSO), with a copper chloride as the catalyst; after the reaction, the solvent is removed by evaporation, and then butyl acetate and water are added into the reaction mixture to obtain an organic phase and an aqueous phase; next, the aqueous phase is removed, and crystallize azoxystrobin from the organic phase by cooling; then, the solid azoxystrobin is obtained by filtering and is washed with methanol, to obtain an azoxystrobin product at 98-99% purity.
The above-mentioned etherification reaction processes in the prior art usually happen in an aprotic polar solvent, the solvent is removed after the reaction, and then an organic solvent is utilized to crystallize the product from the organic solvent. A drawback of those processes is: the high water-solubility of the aprotic polar solvent brings difficulties in the follow-up product separation and recovery procedure; especially, in a case that the solvent of etherification reaction is removed by distillation, the product precipitates heavily after a great part of solvent is removed by distillation; consequently, the stirring in the distillation process is hindered, and the heat transfer in the reaction system is poor; hence, a considerable part of solvent can't be recovered and finally enters into the environment, resulting in increased production cost and environmental pollution. In addition, since the reactant 2-cyanophenol and/or its salt in the above-mentioned etherification reaction process can be oxidized easily and thereby produces tar, and the compound with a structure represented by formula (2) tends to aggregate and hydrolyze, resulting in very low content of azoxystrobin in the crude product obtained from the reaction, usually the product has to be treated with an appropriate solvent for recrystallization in order to obtain a product at higher purity; moreover, the purity of the obtained azoxystrobin product is low, usually lower than 98%. Owing to the fact that azoxystrobin products are heavily applied globally, a huge amount of impurities applied along with azoxystrobin enters into the environment, which brings a potential threat to environmental safety.